Darlene E Berryman1,2,3, Edward O List4,5, Jonathan A Young1,2, Mat Buchman1, Silvana Duran-Ortiz1, Colin Kruse1, Stephen Bell1,2, John J Kopchick1,2. 1. Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA. 2. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 45701, USA. 3. The Diabetes Institute at Ohio University, Ohio University, Athens, OH, 45701, USA. 4. Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA. list@ohio.edu. 5. The Diabetes Institute at Ohio University, Ohio University, Athens, OH, 45701, USA. list@ohio.edu.
Abstract
PURPOSE: Most studies that have examined the transcriptional response to GH have been performed with a single tissue. Thus, the current study performed RNASeq across three insulin-sensitive tissues of GH-treated GH deficient (GHKO) mice. METHODS: GHKO mice were injected with recombinant human GH (hGH) or vehicle daily for 5 days and adipose, liver, and muscle tissues were collected 4 h after the final injection. RNA was isolated from the tissues and sequenced. Genes that were differentially expressed between GH and vehicle treatments were further analyzed. Enrichment analysis and topology-aware pathway analysis were performed. RESULTS: GHKO mice treated with hGH had expected phenotypic alterations, with increased body, fat, fluid, liver, and muscle mass, and increased serum IGF-1 and insulin. 55 Genes were differentially expressed in all three tissues, including the canonical GH targets Igf1, Igfals, and Cish. Enrichment analysis confirmed the canonical GH response in select tissues, such as cell proliferation, metabolism, and fibrosis. The JAK/STAT pathway was the only pathway significantly altered in all three tissues. CONCLUSIONS: As expected, GH caused expression changes of many known target genes, although new candidate GH targets were identified. Liver and muscle appear to be more GH sensitive than adipose tissue due to the larger number of DEG and pathways significantly altered, but adipose still has a characteristic GH response. The diversity of changes uncovered in all three tissues after 5 days of GH treatment highlights the multiplicity of GH's effects in its target tissues.
PURPOSE: Most studies that have examined the transcriptional response to GH have been performed with a single tissue. Thus, the current study performed RNASeq across three insulin-sensitive tissues of GH-treated GH deficient (GHKO) mice. METHODS: GHKO mice were injected with recombinant human GH (hGH) or vehicle daily for 5 days and adipose, liver, and muscle tissues were collected 4 h after the final injection. RNA was isolated from the tissues and sequenced. Genes that were differentially expressed between GH and vehicle treatments were further analyzed. Enrichment analysis and topology-aware pathway analysis were performed. RESULTS: GHKO mice treated with hGH had expected phenotypic alterations, with increased body, fat, fluid, liver, and muscle mass, and increased serum IGF-1 and insulin. 55 Genes were differentially expressed in all three tissues, including the canonical GH targets Igf1, Igfals, and Cish. Enrichment analysis confirmed the canonical GH response in select tissues, such as cell proliferation, metabolism, and fibrosis. The JAK/STAT pathway was the only pathway significantly altered in all three tissues. CONCLUSIONS: As expected, GH caused expression changes of many known target genes, although new candidate GH targets were identified. Liver and muscle appear to be more GH sensitive than adipose tissue due to the larger number of DEG and pathways significantly altered, but adipose still has a characteristic GH response. The diversity of changes uncovered in all three tissues after 5 days of GH treatment highlights the multiplicity of GH's effects in its target tissues.
Authors: Silvana Duran-Ortiz; Jonathan A Young; Adam Jara; Elizabeth A Jensen; Reetobrata Basu; Edward O List; Yanrong Qian; John J Kopchick; Darlene E Berryman Journal: J Neuroendocrinol Date: 2020-10-12 Impact factor: 3.627
Authors: Michael B Stout; William R Swindell; Xu Zhi; Kyle Rohde; Edward O List; Darlene E Berryman; John J Kopchick; Adam Gesing; Yimin Fang; Michal M Masternak Journal: Oncotarget Date: 2015-09-29
Authors: Sebastian Köhler; Leigh Carmody; Nicole Vasilevsky; Julius O B Jacobsen; Daniel Danis; Jean-Philippe Gourdine; Michael Gargano; Nomi L Harris; Nicolas Matentzoglu; Julie A McMurry; David Osumi-Sutherland; Valentina Cipriani; James P Balhoff; Tom Conlin; Hannah Blau; Gareth Baynam; Richard Palmer; Dylan Gratian; Hugh Dawkins; Michael Segal; Anna C Jansen; Ahmed Muaz; Willie H Chang; Jenna Bergerson; Stanley J F Laulederkind; Zafer Yüksel; Sergi Beltran; Alexandra F Freeman; Panagiotis I Sergouniotis; Daniel Durkin; Andrea L Storm; Marc Hanauer; Michael Brudno; Susan M Bello; Murat Sincan; Kayli Rageth; Matthew T Wheeler; Renske Oegema; Halima Lourghi; Maria G Della Rocca; Rachel Thompson; Francisco Castellanos; James Priest; Charlotte Cunningham-Rundles; Ayushi Hegde; Ruth C Lovering; Catherine Hajek; Annie Olry; Luigi Notarangelo; Morgan Similuk; Xingmin A Zhang; David Gómez-Andrés; Hanns Lochmüller; Hélène Dollfus; Sergio Rosenzweig; Shruti Marwaha; Ana Rath; Kathleen Sullivan; Cynthia Smith; Joshua D Milner; Dorothée Leroux; Cornelius F Boerkoel; Amy Klion; Melody C Carter; Tudor Groza; Damian Smedley; Melissa A Haendel; Chris Mungall; Peter N Robinson Journal: Nucleic Acids Res Date: 2019-01-08 Impact factor: 16.971